The risk of loose and “partially unfolded” protein structures as human apolipoprotein A-I (apoA-I) is that they may adopt anomalous conformations, generating insoluble aggregates. In fact, apoA-I fragments can be found in amyloid stores of aortic atherosclerotic plaques as well as in other organs.
The pro-amyloidogenic proteolytic processing may be favored by certain mutations, as Gly26Arg, though neither structural nor environmental factors that trigger it have been deeply investigated.
In order to get insight into the molecular events that favor apoA-I misfolding and aggregation we study, in comparison with the wild type protein, different natural mutants that were detected as inducing amyloidosis in patients.
We analyze environmental factors, especially those related with pro-inflammatory microenvironments (oxidative stress) that favor not only the proteolytic processing but also the anomalous folding. Moreover, we are interested in determining whether protein misfolding can activate the inflammatory cell response and endothelial damage.To do so we have a model of inflammatory response that involves cells of the immune system and endothelial cells.